158,729 research outputs found
Publisher Correction: The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity (Scientific Reports, (2020), 10, 1, (1063), 10.1038/s41598-020-57965-0)
No full textIn the original version of this Article, the author Anna Rita Fetoni was incorrectly indexed. This error has now been corrected
Pioglitazone represents an effective therapeutic target in preventing oxidative/inflammatory cochlear damage induced by noise exposure.
No full textRecent progress in hearing loss research has provided strong evidence for the imbalance of cellular redox status and inflammation as common predominant mechanisms of damage affecting the organ of Corti including noise induced hearing loss. The discovery of a protective molecule acting on both mechanisms is challenging. The thiazolidinediones, a class of antidiabetic drugs including pioglitazone and rosiglitazone, have demonstrated diverse pleiotrophic effects in many tissues where they exhibit anti-inflammatory, anti-proliferative, tissue protective effects and regulators of redox balance acting as agonist of peroxisome proliferator-activated receptors (PPARs). They are members of the family of ligand regulated nuclear hormone receptors that are also expressed in several cochlear cell types, including the outer hair cells. In this study, we investigated the protective capacity of pioglitazone in a model of noise-induced hearing loss in Wistar rats and the molecular mechanisms underlying this protective effects. Specifically, we employed a formulation of pioglitazone in a biocompatible thermogel providing rapid, uniform and sustained inner ear drug delivery via transtympanic injection. Following noise exposure (120 dB, 10 kHz, 1 h), different time schedules of treatment were employed: we explored the efficacy of pioglitazone given immediately (1 h) or at delayed time points (24 and 48 h) after noise exposure and the time course and extent of hearing recovery were assessed. We found that pioglitazone was able to protect auditory function at the mid-high frequencies and to limit cell death in the cochlear basal/middle turn, damaged by noise exposure. Immunofluorescence and western blot analysis provided evidence that pioglitazone mediates both anti-inflammatory and anti-oxidant effects by decreasing NF-κB and IL-1β expression in the cochlea and opposing the oxidative damage induced by noise insult. These results suggest that intratympanic pioglitazone can be considered a valid therapeutic strategy for attenuating noise-induced hearing loss and cochlear damage, reducing inflammatory signaling and restoring cochlear redox balance. Copyright © 2018 Paciello, Fetoni, Rolesi, Wright, Grassi, Troiani and Paludetti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Cisplatin ototoxicity and role of antioxidant on its prevention
No full textObjective: Highlight the novelties of cisplatin ototoxicity and its prevention, focussing on the role of oxidative stress. Methods: We screened various electronic databases and selected the reports concerning clinical data and animal and in vitro models investigations related to cisplatin-induced ototoxicity and or its prevention by antioxidants. Results: Clinical evidence showed that great advances have been made in the chemotherapy outcomes; nevertheless, the ototoxicity, mainly in paediatric patients, is a crucial issue that must be solved. In vitro and in vivo models were pivotal to deeply describe the toxic effect of the cisplatin and which are the mechanisms of action. These knowledges will help the researcher to improve the chemotherapy protocols in order to avoid the adverse effects without compromise the antitumoral action. Conclusion: Antioxidants seem to be the most promising drugs among the large number of substances tested against cisplatin ototoxicity, however, the inflammatory pathway must be taken into consideration
Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL)
No full textThe mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction
EX VIVO GENE THERAPY USING AUTOLOGOUS DERMAL FIBROBLASTS EXPRESSING hLMP3 FOR RAT MANDIBULAR BONE REGENERATION
No full textBACKGROUND: Implantation of autologous skin fibroblasts transduced ex vivo with a replication-defective adenoviral vector, carrying the LIM mineralization protein-3 (Ad-LMP-3), and adsorbed on a hydroxyapatite/collagen (HA/COL) scaffold.
METHODS: Twenty-seven Wistar rats were used. A 5- x 5-mm full-thickness defect was created in the exposed mandible. All animals were randomized into 3 experimental groups: (1) autologous dermal fibroblasts transduced with Ad-LMP-3 and adsorbed on the HA/COL; (2) nontransduced dermal fibroblasts adsorbed on the HA/COL scaffold; and (3) HA/COL scaffold without cells. Three-dimensional micro-CT (3DmicroCT or 3DmuCT) and histological analysis were performed.
RESULTS: Efficient neoosteogenesis was observed in animals treated with LMP-3-expressing cells (group 1) as soon as 4 weeks after surgery. Conversely, nonsignificant bone formation was detected in control animals (groups 2 and 3) at all time points tested.
CONCLUSION: These results suggest that the experimental approach based on transplantation of genetically modified autologous cells could provide an alternative treatment for cranio-maxillo-facial defects. Nonetheless, additional data from the study on larger bone defects must follow to foresee a clinical application in the near future
Acquired sensorineural hearing loss in children: current research and therapeutic perspectives. Sordità infantile acquisita: stato dell’arte della ricerca e prospettive terapeutiche
No full textLa conoscenza dei meccanismi fisiopatologici delle condizioni responsabili dell’ipoacusia acquisita nei bambini, tra cui le infezioni virali
e batteriche, l’esposizione al rumore, l’ototossicità da chemioterapici ed antibiotici aminoglicosidici, è in costante aumento e sta portando
ad un progressivo cambiamento della gestione diagnostica e clinica del bambino ipoacusico. Le infezioni virali rappresentano la causa più
frequente di sordità infantile acquisita, seguita dalla tossicità di antibiotici e chemioterapici; mentre l’esposizione al rumore, soprattutto
negli adolescenti, rappresenta un fattore emergente. Le terapie farmacologiche protettive attualmente in uso includono steroidi, antiossidanti,
antivirali; l’efficacia degli antiossidanti è ancora in fase di conferma clinica anche se vi sono significative evidenze sperimentali,
mentre i farmaci steroidei ed antivirali sono certamente validi seppur la loro tossicità sistemica rappresenti ancora un problema non chiarito
per i quali la somministrazione locale potrebbe rappresentare una possibile evoluzione. Le prospettive di ricerca future includono l’uso
di nanoparticelle per veicolare molecole direttamente nel sito di danno; inoltre, la terapia genica con l’inserimento di materiale genetico
all’interno delle cellule per la cura di condizioni da alterazione del patrimonio genetico con la produzione di proteine normali, potrebbe
svolgere un ruolo rilevante nella cura e soprattutto nella prevenzione delle sordità acquisite; infine, la terapia rigenerativa e l’impianto
delle cellule staminali, nonostante il loro ruolo nell’orecchio interno sia ancora dibattuto, per le notevole limitazioni del loro impiego,
potrebbe trovare un ruolo nei processi riparativi più che nella differenziazione in cellule sensorialiThe knowledge of mechanisms responsible for acquired sensorineural hearing loss in children, such as viral and bacterial infections, noise exposure, aminoglycoside and cisplatin ototoxicity, is increasing and progressively changing the clinical management of affected patients. Viral infections are by far the most relevant cause of acquired hearing loss, followed by aminoglycoside and platinum derivative ototoxicity; moreover, cochlear damage induced by noise overexposure, mainly in adolescents, is an emerging topic. Pharmacological approaches are still challenging to develop a truly effective cochlear protection; however, the use of steroids, antioxidants, antiviral drugs and other small molecules is encouraging for clinical practice. Most of evidence on the effectiveness of antioxidants is still limited to experimental models, while the use of corticosteroids and antiviral drugs has a wide correspondence in literature but with controversial safety. Future therapeutic perspectives include innovative strategies to transport drugs into the cochlea, such as molecules incorporated in nanoparticles that can be delivered to a specific target. Innovative approaches also include the gene therapy designed to compensate for abnormal genes or to make proteins by introducing genetic material into cells; finally, regenerative medicine (including stem cell approaches) may play a central role in the upcoming years in hearing preservation and restoration even if its role in the inner ear is still debate
The protective role of tiopronin in cisplatin ototoxicity in Wistar rats
No full textThe purpose of this study was to evaluate cisplatin-induced ototoxicity and the protective effects of tiopronin. Twenty-four adult Wistar rats served as subjects and were divided into three groups. Eight rats receiving only saline (group A) were used as controls. Eight rats received cisplatin (2 mg/kg) injections (group B) and eight rats received cisplatin and tiopronin (300 mg/kg) (group C) for 8 consecutive days. Both ears of all animals were tested by DPOAE before treatment and on the 4th and 9th days. Seventy-two hours after the final recording session, all animals were killed, and the left cochleas were prepared for electron microscopy and analysed. DPOAE responses were significantly reduced in group B compared to controls (p < 0.05). When tiopronin was added, DPOAE responses were significantly increased compared to those obtained with the administration of cisplatin alone (p < 0.05). The cochleogram showed that tiopronin had a significant protective effect in the basal half and in the lower half of the middle turn. We conclude that tiopronin, a drug effective in protecting against cisplatin nephrotoxicity, is also effective in protecting against cisplatin ototoxicity
Transient evoked otoacoustic emissions (TEOAEs) in new-borns: normative data
No full textObjective: Early diagnosis and rehabilitation of congenital hearing loss are mandatory in order to achieve a satisfactory linguistic and cognitive development. A universal hearing screening in order to identify congenital hearing losses before 3 months of age is required. Methods: TEOAEs are an easy to perform, short lasting, not invasive and low-cost test with a high sensitivity. 320 at term new-borns (640 ears) without any risk factor for hearing loss underwent TEOAEs. The new-borns were screened 3 days after birth. Those who failed the first test were retested when possible before the discharge from the hospital. ABR was performed 3 months later in cases who failed TEOAE. Results: The median TEOAE sampling time was 98 s, the median test duration was 14 min. The mean stimulus amplitude was 80 dB peSPL in the left ear and 81 dB peSPL in the right ear, noise levels within the external meatus during sampling were 44 dB SPL on the right ear and 43 dB SPL on the left one, noise contained within the response (A-B difference) was 8.65 dB SPL in the left ear and 8.74 dB SPL in the right ear, mean TEOAEs amplitudes were 21.49 dB SPL and 21.78 dB SPL in the right and left ear respectively, the mean lower and upper limit of the spectrum being 678 and 5720 Hz. According to these criteria 494/640 ears (77.2%) passed the test at the first recording, while TEOAEs resulted to be absent in 146/640 ears (22.8%). A retest was performed successfully before the discharge from the Hospital in 30/640 ears (4.7%). An ABR recording within the third month of life was scheduled as out-patient in the 58 new-borns (116 ears, 18.2%) who failed the test. 18 of them (36 ears, 5.6%) did not complete the program, 19 new-borns (38 ears, 11.8%) showed a normal ABR, while two new-borns (four ears, 0.6%) failed ABR after 3 months. A second ABR performed after 6 months was normal. Conclusions: TEOAEs recording seems at now the test of choice for a universal hearing screening. However, a greater standardization of criteria both in performing the test and in evaluating the results is needed
Autoimmunity in sudden sensorineural hearing loss: possible role of anti-endothelial cell autoantibodies.
No full textIn order to verify whether anti-endothelial cell autoantibodies (AECAs) can be used as serological markers of inner ear vasculitis in sudden sensorineural hearing loss (SSHL), 32 patients affected by idiopathic SSHL were investigated. All patients underwent a routine general physical examination and extensive audiovestibular, microbiological and immunological investigations. Fourteen normal subjects without a history of HL, autoimmune or metabolic disease served as controls. Detection of AECAs was performed using an indirect immunofluorescence technique. AECA-positive patients were treated with methylprednisone, while AECA-negative patients were treated with a combined regimen of steroids, plasma expander and aspirin. The average hearing recovery for 5 frequencies (0.25-4 kHz) was analyzed in each subject 1 month after treatment and every 3 months thereafter; median follow-up was 12 months (range 9-18 months). A total of 15/32 patients (46.8%; 11/19 females, 4/13 males) were AECA-positive and thus differed significantly from the normal population in whom only 2/14 tested cases were positive (p = 0.03). Severe hearing loss was associated with being AECA-positive in 8/11 cases. During follow-up, 25/32 patients improved their hearing and 17 of these patients were AECA-negative. The seven cases without hearing improvement were all AECA-positive. In patients with SSHL, immune-mediated vascular damage may have a pathogenetic role and AECAs may represent a serological marker of vasculitis even if they are not inner ear-specific and even if they represent an epi-phenomenon rather than the only cause of SSHL
Early Noise-Induced Hearing Loss Accelerates Presbycusis Altering Aging Processes in the Cochlea
No full textSeveral studies identified hearing loss as a risk factor for aging-related processes, including neurodegenerative diseases, as dementia and age-related hearing loss (ARHL). Although the association between hearing impairment in midlife and ARHL has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood. In this study, we used an established animal model of ARHL (C57BL/6 mice) to evaluate if early noise-induced hearing loss (NIHL) could affect the onset or progression of age-related cochlear dysfunction. We found that hearing loss can exacerbate ARHL, damaging sensory-neural cochlear epithelium and causing synaptopathy. Moreover, we studied common pathological markers shared between hearing loss and ARHL, demonstrating that noise exposure can worsen/accelerate redox status imbalance [increase of reactive oxygen species (ROS) production, lipid peroxidation, and dysregulation of endogenous antioxidant response] and vascular dysfunction [increased expression of hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor C (VEGFC)] in the cochlea. Unveiling the molecular mechanisms underlying the link between hearing loss and aging processes could be valuable to identify effective therapeutic strategies to limit the effect of environmental risk factors on age-related diseases
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